Crystal structure of the malic enzyme from Ascaris suum complexed with nicotinamide adenine dinucleotide at 2.3 Å resolution

David E. Coleman, G. S Jagannatha Rao, E. J. Goldsmith, Paul F. Cook, Ben G. Harris

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Abstract

The structure of the Ascaris suum mitochondrial NAD-malic enzyme in binary complex with NAD has been solved to a resolution of 2.3 Å by X-ray crystallography. The structure resembles that of the human mitochondrial enzyme determined in complex with NAD [Xu, Y., Bhargava, G., Wu, H., Loeber, G., and Tong, L. (1999) Structure 7, 877-889]. The enzyme is a tetramer comprised of subunits possessing four domains organized in an "open" structure typical of the NAD-bound form. The subunit organization, as in the human enzyme, is a dimer of dimers. The Ascaris enzyme contains 30 additional residues at its amino terminus relative to the human enzyme. These residues significantly increase the interactions that promote tetramer formation and give rise to different subunit-subunit interactions. Unlike the mammalian enzyme, the Ascaris malic enzyme is not regulated by ATP, and no ATP binding site is observed in this structure. Although the active sites of the two enzymes are similar, residues interacting with NAD differ between the two. The structure is discussed in terms of the mechanism and particularly with respect to previously obtained kinetic and site-directed mutagenesis experiments.

Original languageEnglish (US)
Pages (from-to)6928-6938
Number of pages11
JournalBiochemistry
Volume41
Issue number22
DOIs
StatePublished - Jun 4 2002

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Ascaris suum
NAD
Crystal structure
Enzymes
Ascaris
malate dehydrogenase-(oxaloacetate-decarboxylating) (NAD+)
Dimers
Adenosine Triphosphate
Mutagenesis
X ray crystallography
X Ray Crystallography
Site-Directed Mutagenesis
Catalytic Domain
Binding Sites
Kinetics

ASJC Scopus subject areas

  • Biochemistry

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Crystal structure of the malic enzyme from Ascaris suum complexed with nicotinamide adenine dinucleotide at 2.3 Å resolution. / Coleman, David E.; Rao, G. S Jagannatha; Goldsmith, E. J.; Cook, Paul F.; Harris, Ben G.

In: Biochemistry, Vol. 41, No. 22, 04.06.2002, p. 6928-6938.

Research output: Contribution to journalArticle

Coleman, David E. ; Rao, G. S Jagannatha ; Goldsmith, E. J. ; Cook, Paul F. ; Harris, Ben G. / Crystal structure of the malic enzyme from Ascaris suum complexed with nicotinamide adenine dinucleotide at 2.3 Å resolution. In: Biochemistry. 2002 ; Vol. 41, No. 22. pp. 6928-6938.
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